期刊
ADVANCED MATERIALS
卷 32, 期 4, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201906799
关键词
magnetic resonance imaging (MRI); metastases; signal-amplification; T-1-weighted detection; ultrasmall manganese ferrite nanoparticles
类别
资金
- National Key R&D Program of China [2018YFA0208900, 2018YFE0205300, 2016YFA0201602]
- Innovation Research Group of National Natural Science Foundation [11621505]
- Innovation Program of the Chinese Academy of Sciences [QYZDJ-SSW-SLH022]
- National Natural Science Foundation of China [31800838, 31820103004, 31730032, 31728007, U1505228, U190420008, 31870994, 81771981, 81571809, 31901003]
- Double-First Class Foundation of Materials and Intelligent Manufacturing Discipline of Xiamen University
- Hundred-Talent Program of Chinese Academy of Sciences
Metastasis remains the major cause of death in cancer patients. Thus, there is a need to sensitively detect tumor metastasis, especially ultrasmall metastasis, for early diagnosis and precise treatment of cancer. Herein, an ultrasensitive T-1-weighted magnetic resonance imaging (MRI) contrast agent, UMFNP-CREKA is reported. By conjugating the ultrasmall manganese ferrite nanoparticles (UMFNPs) with a tumor-targeting penta-peptide CREKA (Cys-Arg-Glu-Lys-Ala), ultrasmall breast cancer metastases are accurately detected. With a behavior similar to neutrophils' immunosurveillance process for eliminating foreign pathogens, UMFNP-CREKA exhibits a chemotactic targeting-activation capacity. UMFNP-CREKA is recruited to the margin of tumor metastases by the binding of CREKA with fibrin-fibronectin complexes, which are abundant around tumors, and then release of manganese ions (Mn2+) to the metastasis in response to pathological parameters (mild acidity and elevated H2O2). The localized release of Mn2+ and its interaction with proteins affects a marked amplification of T-1-weighted magnetic resonance (MR) signals. In vivo T-1-weighted MRI experiments reveal that UMFNP-CREKA can detect metastases at an unprecedented minimum detection limit of 0.39 mm, which has significantly extended the detection limit of previously reported MRI probe.
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